Detecting an Early Response to Donepezil With Measures of Visual Attention

• Sponsor: NYU Langone Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT03073876
• Collaborator: Queens College, The City University of New York (Other)
• Enrollment: 25
• Location: 1
• Arms: 2
• Actual Duration (Months): 181.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Acetylcholinesterase inhibitors (AChE-I) comprise a class of drugs used to treat Alzheimer's disease (AD), but controversy about their usefulness remains. Modest response rates of treated versus placebo groups, small effect sizes with respect to efficacy, drug costs, and clinical relevance of the effects are problematic. Standard efficacy measures of efficacy are not sufficiently sensitive, and trying to assess cognitive change after 4-6 months of therapy confounds the drug effect and the natural progression of the disease.

Surprisingly, attention has never been included in the assessment of AChE-I drugs. The rationale for using attentional measures are that (1) Attentional deficits are recognized as a critical cognitive change in the earliest phases of AD; (2) Attentional function is directly mediated by the cholinergic system, and responds rapidly to cholinergic augmentation, particularly on tasks that tax available attentional capacity are dose dependent; and (3) Acetylcholine is depleted in AD. However, the link between attention and cholinergic depletion in AD has not been fully explored, especially with regard to response to cholinergic treatment.

The study tests if attentional performance can be a more sensitive marker of response. In a longitudinal study we measure attentional, as well as cognitive and behavioral performance in de novo AD patients undergoing donepezil treatment. The investigators develop visual attentional measures and contrast them to global and domain-specific cognitive scores on three occasions (T1) baseline pre-treatment, (T2) after approximately 6 weeks, and (T3) after 6 months treatment. The T1-to-T2 arm is a double-blind placebo control period, after which members of the placebo group start open-label treatment. The assessment at 6 months allows us to determine whether the changes seen earlier at T2 can predict patients who respond, or determine which measures best predict response.

We hypothesize that attention measures are more sensitive than standard global measures or other cognitive domains and that the change of attentional function can be detected after only after approximately 6 weeks treatment.

Knowledge from this project will facilitate and inform our decisions about individual patients undergoing pharmacological treatment.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer Disease	Drug: Donepezil Hydrochloride; Drug: Placebo	Phase 4

Detailed Description

Acetylcholinesterase inhibitors (AChE-I) comprise the major class of drugs used to treat Alzheimer's disease (AD). Despite widespread use, there is controversy about the usefulness of these medications. Concerns have been modest response rates of treated versus placebo groups, relatively small effect sizes with respect to efficacy, drug costs, and clinical relevance of the effects. One problem is that measures of efficacy used may not be sufficiently sensitive to detect a true drug effect. Another problem is that changes noted after 4-6 months of therapy confound the drug effect and the natural progression of the disease. Lastly, patient heterogeneity may contribute to the wide range of degree of response, further decreasing overall effect sizes. The investigators address three important issues to improve the clinical usefulness of cholinergic therapy. First, outcome measures are needed that are sensitive to the effects of cholinergic treatment. Second, outcome measures should be sensitive to the drug effect early in the course of treatment before a measurable decline of the disease progression occurs. Third, improved treatment would be attained if specific patient characteristics or performance measures were identified, which contributed to, or even predicted who will likely benefit. The premise of the current proposal is that measures of higher-order attention - currently omitted from standard assessments of treatment outcome - can provide insight into early efficacy of cholinergic treatment. The investigators are conducting a preliminary study that supports our hypotheses by testing the value of such attentional measures. The rationale for using attentional measures is as follows: (1) Attentional deficits are recognized as a critical cognitive change in the earliest phases of AD; (2) Attentional function, particularly tasks that tax available attentional capacity, is mediated by the cholinergic system; and (3) Acetylcholine is depleted in AD. However, the link between attention and cholinergic depletion in AD has not been fully explored, particularly with regard to response to cholinergic treatment. Surprisingly, attentional measures have not been included in the evaluation of AChE-I in the treatment of AD. The investigators propose that attentional performance could serve as a highly sensitive outcome measure and a marker of response.

Study aims and hypotheses

1. To determine that higher-order attentional measures are sensitive to the effect of cholinergic change early in the course of treatment. The investigators predict that performance on attentional tasks will improve in AChE-I treated patients compared to placebo controls after 7±1 weeks of treatment.

2. 2a. To examine the effect of cholinergic treatment on attentional measures as compared with global measures or measures of other cognitive domains. The investigators predict that the performance on tasks of attention is more sensitive than traditional global measures of performance.

2b. To examine whether cholinergic treatment changes the relationships among measures of attention and measures of other cognitive function. The prediction is that that the relationships among attention and cognitive domain measures will change with treatment.

1. To determine whether performance at 7±1 weeks can predict response at 6 months 3a. Patient response to AChE-I may be influenced by demographic variables, or influence performance in one or more cognitive domains. The aim is to determine which cognitive domain or demographic characteristic best predicts treatment response at six months. It is hypothesized that attention and memory (both mediated by cholinergic mechanisms) will best predict treatment response seen at six months.

3b. To determine whether an attentional change seen in patients early in the treatment course predicts drug response. It is hypothesized that change in attention measured between baseline and 7±1 weeks will predict overall improvement in those patients who show positive treatment response at six months.

Knowledge gained from this project will facilitate and inform our decisions about individual patients undergoing pharmacological treatment. The application of these goals can apply to current AChE-I treatment as well as other treatments, such as those now involving combined cholinergic and glutaminergic agents.

BACKGROUND AND SIGNIFICANCE Attention and Alzheimer's disease (AD): The vulnerability of higher-order attention tasks in AD occurs in tasks such as selective attention, and covert orienting. Attentional deficits are documented in patients with prodromal AD who later develop the disease, suggesting potential sensitivity of attention to disease onset. Mechanisms of attention are mediated via anterior executive control (required in conjunctive search and inhibitory control) and via posterior disengagement. The deficits in AD may be explained by regional frontal or posterior dysfunction, or by a disconnection between the frontal and posterior attentional networks that disrupt the feedback system. Acetylcholine and attention: A primary modulator of attention is acetylcholine (ACh). Decreased ACh impairs attentional function in animals and humans including vigilance in rat, covert orienting in primate and AD, and complex attention in human airplane pilots. ACh functions in a dose related manner, with increased task load of higher background noise correlating with increased ACh release. Cholinergic antagonists (e.g., scopolamine) slow reaction time (RT) and increase omission errors on visual search, and increase omission and commission errors on signal detection. Higher scopolamine doses slow RT in covert orienting in primates involving inferior parietal regions.

AD, attention and cholinesterase inhibitors: The relationship between attention and acetylcholine has not been well demonstrated in the assessment of AChE-I. Efficacy studies of donepezil, galantamine or rivastigmine show modest effect sizes ranging from 1.8-4.1 points on the 70 point Alzheimer Disease Assessment Scale - Cognitive section (ADAS-Cog) scale. These small effect sizes may partially be a function of using this outcome measure, which obscures the sensitivity to attention and memory with a global score. Targeted cognitive domains may be better response indicators. In a post-mortem analysis of AD patients, regions of low cholinergic activity correlated to memory and attention.

Moreover, after 12 weeks of galantamine treatment, AD patients who reached therapeutic dose showed faster RT, better choice reaction time and in memory, recognition of faces. Also, on functional imaging, early response to AChE-I appears to affect regions that mediate directed attention.

In summary, if attentional function is intrinsically linked to the level of cholinergic activity, it should used be an outcome measure of AChE-I treatment in AD to improve treatment sensitivity.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Double Blind Placebo ControlDouble Blind Placebo Control
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Study drug was prepared by research pharmacist who was the only person privy to group assignment. Drug and Placebo pills looked identical.
• Primary Purpose: Other
• Official Title: Detecting an Early Response to Donepezil With Measures of Visual Attention
• Actual Study Start Date: Dec 1, 2005
• Actual Primary Completion Date: Jul 31, 2009
• Actual Study Completion Date: Jan 13, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Drug Participants in the Drug group received oral 5mg of Donepezil Hydrochloride daily for 6 months. The Drug group was assessed at baseline, after approximately 6 weeks and after 6 months of treatment. The baseline to 6 weeks phase was part of the double-blind, placebo controlled portion of the trial.	Drug: Donepezil Hydrochloride; 5mg of Donepezil Hydrochloride by mouth; Other Names: Aricept
Placebo Comparator: Placebo Participants in the placebo group first received oral administration of a placebo pill for approximately 6 weeks. After that initial interval, the study was unblinded and participants in the placebo group then received 5mg of donepezil hydrochloride treatment for 6 months. The Placebo group was evaluated at baseline, after 6 weeks of placebo, after 6 weeks of donepezil hydrochloride drug treatment, and 6 months of donepezil hydrochloride treatment.	Drug: Donepezil Hydrochloride; 5mg of Donepezil Hydrochloride by mouth; Other Names: Aricept ; Drug: Placebo; prepared placebo looking exactly the same as drug. Participants took placebo by mouth for approximately 6 weeks, and after unblinding, they took donepezil hydrochloride for 6 months.; Other Names: Placebo pill

Outcome Measures

Primary Outcome Measures

1. Change in Foreperiod Effect Task - Processing Speed [Baseline to 6 weeks]

   Computerized attention task measures response time to detect a target presented at varied interstimulus intervals (350ms and 500ms). Participants respond to centrally presented asterisk on computer screen. Time elapsed from prior stimulus (= interstimulus interval) indicates when prior stimulus was presented. xx

2. Change in Covert Orienting Task [Baseline to 6 weeks]

   Computerized attention task measuring response time to detect a target after a spatial orienting cues of either valid (cue on same side in space as target) or Invalid Cue (cue on opposite side of space as target). Longer response time (msec) indicates worse performance.

3. Change in Attentional Blink Task Baseline to 6 Weeks - Stimulus Onset Asynchrony (SOA) 266ms [Baseline to 6 weeks]

   Computerized attention task measures the accuracy of reporting stimuli presented at time intervals, varying load. Faster reaction time and accuracy represents better performance.

4. Change in Attentional Blink Task Baseline to 6 Weeks - SOA 399ms [Baseline to 6 weeks]

   Computerized attention task measures the accuracy of reporting stimuli presented within 399 ms interval. Higher accuracy represents better performance.

5. Change of ADAS-COG From Baseline to 6 Months [Baseline to 6 months]

   Change of Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog); primary outcome measure of drug efficacy. Minimum value = 0, maximum value = 70. Higher scores represent worse cognitive functioning.

6. Foreperiod Effect Task at 6 Weeks - Fatigue (Blocks 1 & 2) [6 weeks]

   Computerized attention task measures reaction time (RT) to detect a target presented at varied interstimulus interval comparing Block 1 (presented at beginning of session) and Block 2 (presented at end of session)

7. Change in Foreperiod Effect Task - Variability (350ms & 500ms) [Baseline to 6 weeks]

   Computerized attention task measures the variability (SD) in response time to detect a target presented at varied interstimulus intervals (350ms and 500ms)

8. Covert Orienting at 6 Weeks - Fatigue Across Blocks [6 weeks]

   Computerized attention task measures response time to detect a target across blocks of stimuli. Data shown for performance at Block1 and Block5

9. Neuropsychiatric Inventory Score [6 months]

   Neuropsychiatric Inventory (NPI) is a scale that measures neuropsychiatric symptoms. We reported a score that captures the frequency of each symptom multiplied by the severity rating score. Scores range from 0 - 144; Higher scores represent worse outcomes.

10. Instrumental Activities of Daily Living [6 months]

    Scale of instrumental activities of daily living (IADLs), adapted from Lawton Brody scale. Caregiver rates 8 functional items from 0-2 severity. Total score is the sum of ratings for each item. Total score ranges from 0 (minimum) to 16 (maximum) with higher scores representing worse functional outcomes.

Secondary Outcome Measures

1. Change in Dementia Rating Scale [Baseline to 6 weeks]

   Dementia Rating Scale (DRS) change score (performance at 6 weeks minus performance at baseline). This is a global measure of cognitive function. Scores range from 0 - 144; higher scores represent better cognitive functioning.

2. Mini Mental Status Examination [Baseline to 6 weeks]

   Mini Mental Status Examination (MMSE) is a commonly used cognitive screener. Scores range from 0-30; higher scores mean better cognitive functioning.

3. Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) [Baseline to 6 weeks]

   Change of Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog); primary outcome measure of drug efficacy. Minimum value = 0, maximum value = 70. Higher scores represent worse cognitive functioning.

4. Change in Digit Span Forward [Baseline to 6 weeks]

   This measure represents the change in the variable longest Digit Span Forward (LDSF) from baseline to 6 weeks. Score represents the maximum length of number repeated in the forward condition. Score ranges from 0 to 9. Higher scores represent better outcome.

5. Change in Hopkins Verbal Learning Test- Revised - Recall [Baseline to 6 weeks]

   Hopkins Verbal Learning Test- Revised (HVLT-R) (Brandt, 1991) is a list-learning task. Recall variable is computed by adding the number of words repeated in each of the three learning trials. Raw scores of each measure were used in the analyses. Total Recall ranges from 0-30. Higher scores represent better outcome.

6. Change in Language Function Assessed With the Letter Fluency Test [Baseline to 6 weeks]

   Letter fluency (FAS) (Benton, 1967) was selected to assess speed of verbal generativity. Participants are required to generate words that start with a particular letter (excluding n; three trials (words starting with 'F', 'A', 'S' each for 1 minute minutes) are administered. Higher performance is better with range from 0 to unlimited.

7. Change on Trail Making Test - Condition [Baseline to 6 weeks]

   The Delis-Kaplan Executive Function (D-KEFS Trail) Subtest 4: Number-Letter Switching Scaled Score was used to assess executive functioning. Scaled scores range from 1-19. Higher scores represent less impairment (below 8 = low; 8-12 = average; > 12 = above average). Scores represent seconds to complete the task. Faster performance is better.

8. Change in Visual Form Discrimination [Baseline to 6 weeks]

   Measure of visuospatial function requiring matching designs from the Benton Visual Form Discrimination test. Total scores is calculated by adding the number of items correct. Total score ranges from 0-32, higher score is better.

9. Change in Category Fluency Test [Baseline to 6 weeks]

   Measure of language / semantic function. This task requires participants to generate words belonging to specific categories within 1 minute. There are three trials. Total scores is computed by obtaining the mean number of words generated across the three trials (fruits/vegetables/animals). Higher score represents better outcome.

10. Change in Digit Span Backwards [Baseline to 6 weeks]

    This measure represents the change in the variable longest Digit Span Backwards (LDSB) from baseline to 6 weeks. Score represents the maximum length of number repeated in the backward condition. Score ranges from 0 to 8. Higher scores represent better outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 95 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Clinical diagnosis of Alzheimer's Disease

• Mini Mental State Examination score >15 / 30

• Can swallow pills

Exclusion Criteria:

• No other dementia due to Parkinson's disease, Lewy Body dementia, Normal Pressure Hydrocephalus, Fronto-temporal dementia, or prominent cerebral vascular accident

• No prior or concurrent use of cholinesterase inhibitors

• No prior or concurrent use of memantine hydrochloride

• No other concurrent anticholinergic treatments

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Winthrop-University Hospital	Mineola	New York	United States	11501

Sponsors and Collaborators

• NYU Langone Health
• Queens College, The City University of New York

Investigators

• Principal Investigator: Nancy Foldi, PhD, NYU Winthrop Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 7, 2006

More Information

Publications

None provided.

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT03073876
• Other Study ID Numbers: WUH 05030
• First Posted: Mar 8, 2017
• Last Update Posted: Feb 4, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by NYU Langone Health: Alzheimer Disease; Attention; Donepezil hydrochloride
• Additional relevant MeSH terms: Alzheimer Disease; Donepezil

Study Results

Participant Flow

Recruitment Details	Of 25 individuals enrolled, 2 participants allocated to the placebo group discontinued: one complained of side-effects (n = 1); one moved from NY area (n = 1). Total N= 23.

Arm/Group Title	Drug	Placebo
Arm/Group Description	Participants in the Drug group received oral 5mg of Donepezil Hydrochloride daily for 6 months. The Drug group was assessed at baseline, after approximately 6 weeks and after 6 months of treatment. The baseline to 6 weeks phase was part of the double-blind, placebo controlled portion of the trial. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth	Participants in the placebo group first received oral administration of a placebo pill for approximately 6 weeks. After that initial interval, the study was unblinded and participants in the placebo group then received 5mg of donepezil hydrochloride treatment for 6 months. The Placebo group was evaluated at baseline, after 6 weeks of placebo, after 6 weeks of donepezil hydrochloride drug treatment, and 6 months of donepezil hydrochloride treatment. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth Placebo: prepared placebo looking exactly the same as drug. Participants took placebo by mouth for approximately 6 weeks, and after unblinding, they took donepezil hydrochloride for 6 months.
Period Title: Overall Study
STARTED	12	11
COMPLETED	12	11
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Drug	Placebo	Total
Arm/Group Description	Participants in the Drug group received oral 5mg of Donepezil Hydrochloride daily for 6 months. The Drug group was assessed at baseline, after approximately 6 weeks and after 6 months of treatment. The baseline to 6 weeks phase was part of the double-blind, placebo controlled portion of the trial. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth	Participants in the placebo group first received oral administration of a placebo pill for approximately 6 weeks. After that initial interval, the study was unblinded and participants in the placebo group then received 5mg of donepezil hydrochloride treatment for 6 months. The Placebo group was evaluated at baseline, after 6 weeks of placebo, after 6 weeks of donepezil hydrochloride drug treatment, and 6 months of donepezil hydrochloride treatment. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth Placebo: prepared placebo looking exactly the same as drug. Participants took placebo by mouth for approximately 6 weeks, and after unblinding, they took donepezil hydrochloride for 6 months.	Total of all reporting groups
Overall Participants	12	11	23
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 100%	11 100%	23 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	8 66.7%	7 63.6%	15 65.2%
Male	4 33.3%	4 36.4%	8 34.8%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	12 100%	11 100%	23 100%
Region of Enrollment (participants) [Number]
United States	12 100%	11 100%	23 100%
Mini Mental State Examination (MMSE) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	24.3 (3.5)	25.4 (1.7)	24.9 (2.6)
Dementia Rating Scale (DRS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	119.7 (10.4)	127.1 (7.2)	123.4 (8.8)
Clinical Dementia Rating Scale (CDRS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	1 (.4)	3 (.4)	1.9 (.41)
Geriatric Depression Scale (GDS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	6.7 (6.2)	6.5 (4.5)	6.6 (5.4)
Neuropsychiatric Inventory (NPI) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	16.7 (12.3)	15.4 (15.8)	16.1 (14.1)
ADAS- Cog (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	17.3 (6.6)	13.1 (3.8)	15.2 (5.2)
HVLT Learning (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	11 (2.6)	11.4 (3.8)	11.2 (3.2)
HVLT delay Recall (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	1.2 (1)	1.1 (1.4)	1.1 (1.2)
HVLT Recognition (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	5.3 (3.6)	6.7 (2.7)	6.0 (3.15)
Letter Fluency (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	9.0 (5.0)	9.4 (4.3)	9.2 (4.6)
Category Fluency (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	7.4 (2.7)	7.9 (2.7)	7.5 (2.7)
Visual Form Discrimination (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	26.7 (3.9)	27.9 (2.5)	27.3 (3.2)
Digit Span Forward (max) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	5.9 (0.9)	6.0 (0.8)	5.9 (0.8)
Digit Span Backward (max) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	3.6 (0.8)	6.0 (0.8)	4.8 (0.8)
DKEFS Trail Making Test-4 (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	12.2 (11.7)	6.7 (6.2)	9.5 (8.9)
DKEFS Trail Making Test-5 (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	62.7 (36.5)	54.3 (16.6)	58.5 (26.6)

Outcome Measures

1. Primary Outcome

Title	Change in Foreperiod Effect Task - Processing Speed
Description	Computerized attention task measures response time to detect a target presented at varied interstimulus intervals (350ms and 500ms). Participants respond to centrally presented asterisk on computer screen. Time elapsed from prior stimulus (= interstimulus interval) indicates when prior stimulus was presented. xx
Time Frame	Baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Drug	Placebo
Arm/Group Description	Participants in the Drug group received oral 5mg of Donepezil Hydrochloride daily for 6 months. The Drug group was assessed at baseline, after approximately 6 weeks and after 6 months of treatment. The baseline to 6 weeks phase was part of the double-blind, placebo controlled portion of the trial. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth	Participants in the placebo group first received oral administration of a placebo pill for approximately 6 weeks. After that initial interval, the study was unblinded and participants in the placebo group then received 5mg of donepezil hydrochloride treatment for 6 months. The Placebo group was evaluated at baseline, after 6 weeks of placebo, after 6 weeks of donepezil hydrochloride drug treatment, and 6 months of donepezil hydrochloride treatment. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth Placebo: prepared placebo looking exactly the same as drug. Participants took placebo by mouth for approximately 6 weeks, and after unblinding, they took donepezil hydrochloride for 6 months.
Measure Participants	12	11
350	42 (176.3)	13 (9)
500	33 (176.7)	13 (9)

2. Primary Outcome

Title	Change in Covert Orienting Task
Description	Computerized attention task measuring response time to detect a target after a spatial orienting cues of either valid (cue on same side in space as target) or Invalid Cue (cue on opposite side of space as target). Longer response time (msec) indicates worse performance.
Time Frame	Baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Drug	Placebo
Arm/Group Description	treatment group	placebo group
Measure Participants	11	12
Median (Inter-Quartile Range) [milliseconds]	496.5	452.5

3. Primary Outcome

Title	Change in Attentional Blink Task Baseline to 6 Weeks - Stimulus Onset Asynchrony (SOA) 266ms
Description	Computerized attention task measures the accuracy of reporting stimuli presented at time intervals, varying load. Faster reaction time and accuracy represents better performance.
Time Frame	Baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Drug Treatment
Arm/Group Description	All Participants received Donepezil Hydrochloride daily for 6 weeks. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth
Measure Participants	23
Mean (Standard Deviation) [milliseconds]	-.06 (.32)

4. Primary Outcome

Title	Change in Attentional Blink Task Baseline to 6 Weeks - SOA 399ms
Description	Computerized attention task measures the accuracy of reporting stimuli presented within 399 ms interval. Higher accuracy represents better performance.
Time Frame	Baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Drug Treatment
Arm/Group Description	All Participants received Donepezil Hydrochloride daily for 6 weeks. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth
Measure Participants	23
Mean (Standard Deviation) [milliseconds]	-.022 (.33)

5. Primary Outcome

Title	Change of ADAS-COG From Baseline to 6 Months
Description	Change of Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog); primary outcome measure of drug efficacy. Minimum value = 0, maximum value = 70. Higher scores represent worse cognitive functioning.
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Drug Treatment
Arm/Group Description	All Participants received Donepezil Hydrochloride daily for 6 months. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth
Measure Participants	23
Mean (Standard Deviation) [units on a scale]	-.29 (4.70)

6. Primary Outcome

Title	Foreperiod Effect Task at 6 Weeks - Fatigue (Blocks 1 & 2)
Description	Computerized attention task measures reaction time (RT) to detect a target presented at varied interstimulus interval comparing Block 1 (presented at beginning of session) and Block 2 (presented at end of session)
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Drug	Placebo
Arm/Group Description	Participants in the Drug group received oral 5mg of Donepezil Hydrochloride daily for 6 months. The Drug group was assessed at baseline, after approximately 6 weeks and after 6 months of treatment. The baseline to 6 weeks phase was part of the double-blind, placebo controlled portion of the trial. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth	Participants in the placebo group first received oral administration of a placebo pill for approximately 6 weeks. After that initial interval, the study was unblinded and participants in the placebo group then received 5mg of donepezil hydrochloride treatment for 6 months. The Placebo group was evaluated at baseline, after 6 weeks of placebo, after 6 weeks of donepezil hydrochloride drug treatment, and 6 months of donepezil hydrochloride treatment. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth Placebo: prepared placebo looking exactly the same as drug. Participants took placebo by mouth for approximately 6 weeks, and after unblinding, they took donepezil hydrochloride for 6 months.
Measure Participants	12	11
Block 1	400 (87.4)	331 (200.7)
Block 2	395 (85.3)	385 (254.2)

7. Primary Outcome

Title	Change in Foreperiod Effect Task - Variability (350ms & 500ms)
Description	Computerized attention task measures the variability (SD) in response time to detect a target presented at varied interstimulus intervals (350ms and 500ms)
Time Frame	Baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Drug	Placebo
Arm/Group Description	Participants in the Drug group received oral 5mg of Donepezil Hydrochloride daily for 6 months. The Drug group was assessed at baseline, after approximately 6 weeks and after 6 months of treatment. The baseline to 6 weeks phase was part of the double-blind, placebo controlled portion of the trial. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth	Participants in the placebo group first received oral administration of a placebo pill for approximately 6 weeks. After that initial interval, the study was unblinded and participants in the placebo group then received 5mg of donepezil hydrochloride treatment for 6 months. The Placebo group was evaluated at baseline, after 6 weeks of placebo, after 6 weeks of donepezil hydrochloride drug treatment, and 6 months of donepezil hydrochloride treatment. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth Placebo: prepared placebo looking exactly the same as drug. Participants took placebo by mouth for approximately 6 weeks, and after unblinding, they took donepezil hydrochloride for 6 months.
Measure Participants	12	10
350ms	-26.7 (42.97)	-4.5 (34.44)
500ms	28.46 (110.63)	8.37 (39.73)

8. Primary Outcome

Title	Covert Orienting at 6 Weeks - Fatigue Across Blocks
Description	Computerized attention task measures response time to detect a target across blocks of stimuli. Data shown for performance at Block1 and Block5
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Drug	Placebo
Arm/Group Description	Participants in the Drug group received oral 5mg of Donepezil Hydrochloride daily for 6 months. The Drug group was assessed at baseline, after approximately 6 weeks and after 6 months of treatment. The baseline to 6 weeks phase was part of the double-blind, placebo controlled portion of the trial. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth	Participants in the placebo group first received oral administration of a placebo pill for approximately 6 weeks. After that initial interval, the study was unblinded and participants in the placebo group then received 5mg of donepezil hydrochloride treatment for 6 months. The Placebo group was evaluated at baseline, after 6 weeks of placebo, after 6 weeks of donepezil hydrochloride drug treatment, and 6 months of donepezil hydrochloride treatment. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth Placebo: prepared placebo looking exactly the same as drug. Participants took placebo by mouth for approximately 6 weeks, and after unblinding, they took donepezil hydrochloride for 6 months.
Measure Participants	12	11
Block 1	415 (145.1)	402 (95.1)
Block 5	451 (134.2)	487 (144.3)

9. Primary Outcome

Title	Neuropsychiatric Inventory Score
Description	Neuropsychiatric Inventory (NPI) is a scale that measures neuropsychiatric symptoms. We reported a score that captures the frequency of each symptom multiplied by the severity rating score. Scores range from 0 - 144; Higher scores represent worse outcomes.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Drug Treatment
Arm/Group Description	All Participants received Donepezil Hydrochloride daily for 6 months. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth
Measure Participants	23
Mean (Standard Deviation) [score on a scale]	14.09 (14.26)

10. Secondary Outcome

Title	Change in Dementia Rating Scale
Description	Dementia Rating Scale (DRS) change score (performance at 6 weeks minus performance at baseline). This is a global measure of cognitive function. Scores range from 0 - 144; higher scores represent better cognitive functioning.
Time Frame	Baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Drug	Placebo
Arm/Group Description	Participants in the Drug group received oral 5mg of Donepezil Hydrochloride daily for 6 months. The Drug group was assessed at baseline, after approximately 6 weeks and after 6 months of treatment. The baseline to 6 weeks phase was part of the double-blind, placebo controlled portion of the trial. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth	Participants in the placebo group first received oral administration of a placebo pill for approximately 6 weeks. After that initial interval, the study was unblinded and participants in the placebo group then received 5mg of donepezil hydrochloride treatment for 6 months. The Placebo group was evaluated at baseline, after 6 weeks of placebo, after 6 weeks of donepezil hydrochloride drug treatment, and 6 months of donepezil hydrochloride treatment. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth Placebo: prepared placebo looking exactly the same as drug. Participants took placebo by mouth for approximately 6 weeks, and after unblinding, they took donepezil hydrochloride for 6 months.
Measure Participants	12	11
Mean (Standard Deviation) [units on a scale]	1.67 (6.91)	-.54 (6.27)

11. Secondary Outcome

Title	Mini Mental Status Examination
Description	Mini Mental Status Examination (MMSE) is a commonly used cognitive screener. Scores range from 0-30; higher scores mean better cognitive functioning.
Time Frame	Baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Drug	Placebo
Arm/Group Description	Participants in the Drug group received oral 5mg of Donepezil Hydrochloride daily for 6 months. The Drug group was assessed at baseline, after approximately 6 weeks and after 6 months of treatment. The baseline to 6 weeks phase was part of the double-blind, placebo controlled portion of the trial. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth	Participants in the placebo group first received oral administration of a placebo pill for approximately 6 weeks. After that initial interval, the study was unblinded and participants in the placebo group then received 5mg of donepezil hydrochloride treatment for 6 months. The Placebo group was evaluated at baseline, after 6 weeks of placebo, after 6 weeks of donepezil hydrochloride drug treatment, and 6 months of donepezil hydrochloride treatment. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth Placebo: prepared placebo looking exactly the same as drug. Participants took placebo by mouth for approximately 6 weeks, and after unblinding, they took donepezil hydrochloride for 6 months.
Measure Participants	12	10
Mean (Standard Deviation) [units on a scale]	-.17 (2.44)	-1.09 (2.02)

12. Secondary Outcome

Title	Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog)
Description	Change of Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog); primary outcome measure of drug efficacy. Minimum value = 0, maximum value = 70. Higher scores represent worse cognitive functioning.
Time Frame	Baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Drug	Placebo
Arm/Group Description	Participants in the Drug group received oral 5mg of Donepezil Hydrochloride daily for 6 months. The Drug group was assessed at baseline, after approximately 6 weeks and after 6 months of treatment. The baseline to 6 weeks phase was part of the double-blind, placebo controlled portion of the trial. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth	Participants in the placebo group first received oral administration of a placebo pill for approximately 6 weeks. After that initial interval, the study was unblinded and participants in the placebo group then received 5mg of donepezil hydrochloride treatment for 6 months. The Placebo group was evaluated at baseline, after 6 weeks of placebo, after 6 weeks of donepezil hydrochloride drug treatment, and 6 months of donepezil hydrochloride treatment. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth Placebo: prepared placebo looking exactly the same as drug. Participants took placebo by mouth for approximately 6 weeks, and after unblinding, they took donepezil hydrochloride for 6 months.
Measure Participants	12	10
Mean (Standard Deviation) [score on a scale]	-1.90 (4.92)	.99 (2.25)

13. Secondary Outcome

Title	Change in Digit Span Forward
Description	This measure represents the change in the variable longest Digit Span Forward (LDSF) from baseline to 6 weeks. Score represents the maximum length of number repeated in the forward condition. Score ranges from 0 to 9. Higher scores represent better outcome.
Time Frame	Baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Drug	Placebo
Arm/Group Description	Participants in the Drug group received oral 5mg of Donepezil Hydrochloride daily for 6 months. The Drug group was assessed at baseline, after approximately 6 weeks and after 6 months of treatment. The baseline to 6 weeks phase was part of the double-blind, placebo controlled portion of the trial. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth	Participants in the placebo group first received oral administration of a placebo pill for approximately 6 weeks. After that initial interval, the study was unblinded and participants in the placebo group then received 5mg of donepezil hydrochloride treatment for 6 months. The Placebo group was evaluated at baseline, after 6 weeks of placebo, after 6 weeks of donepezil hydrochloride drug treatment, and 6 months of donepezil hydrochloride treatment. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth Placebo: prepared placebo looking exactly the same as drug. Participants took placebo by mouth for approximately 6 weeks, and after unblinding, they took donepezil hydrochloride for 6 months.
Measure Participants	12	10
Mean (Standard Deviation) [units on a scale]	-0.6 (1)	-0.4 (0.75)

14. Secondary Outcome

Title	Change in Hopkins Verbal Learning Test- Revised - Recall
Description	Hopkins Verbal Learning Test- Revised (HVLT-R) (Brandt, 1991) is a list-learning task. Recall variable is computed by adding the number of words repeated in each of the three learning trials. Raw scores of each measure were used in the analyses. Total Recall ranges from 0-30. Higher scores represent better outcome.
Time Frame	Baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Drug	Placebo
Arm/Group Description	Participants in the Drug group received oral 5mg of Donepezil Hydrochloride daily for 6 months. The Drug group was assessed at baseline, after approximately 6 weeks and after 6 months of treatment. The baseline to 6 weeks phase was part of the double-blind, placebo controlled portion of the trial. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth	Participants in the placebo group first received oral administration of a placebo pill for approximately 6 weeks. After that initial interval, the study was unblinded and participants in the placebo group then received 5mg of donepezil hydrochloride treatment for 6 months. The Placebo group was evaluated at baseline, after 6 weeks of placebo, after 6 weeks of donepezil hydrochloride drug treatment, and 6 months of donepezil hydrochloride treatment. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth Placebo: prepared placebo looking exactly the same as drug. Participants took placebo by mouth for approximately 6 weeks, and after unblinding, they took donepezil hydrochloride for 6 months.
Measure Participants	12	10
Mean (Standard Deviation) [score on a scale]	.17 (1.8)	.40 (4.79)

15. Secondary Outcome

Title	Change in Language Function Assessed With the Letter Fluency Test
Description	Letter fluency (FAS) (Benton, 1967) was selected to assess speed of verbal generativity. Participants are required to generate words that start with a particular letter (excluding n; three trials (words starting with 'F', 'A', 'S' each for 1 minute minutes) are administered. Higher performance is better with range from 0 to unlimited.
Time Frame	Baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Drug	Placebo
Arm/Group Description	Participants in the Drug group received oral 5mg of Donepezil Hydrochloride daily for 6 months. The Drug group was assessed at baseline, after approximately 6 weeks. The baseline to 6 weeks phase was part of the double-blind, placebo controlled portion of the trial. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth	Participants in the placebo group first received oral administration of a placebo pill for approximately 6 weeks. After that initial interval, the study was unblinded and participants in the placebo group then received 5mg of donepezil hydrochloride treatment for 6 months. The Placebo group was evaluated at baseline, after 6 weeks of placebo, after 6 weeks of donepezil hydrochloride drug treatment, and 6 months of donepezil hydrochloride treatment. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth Placebo: prepared placebo looking exactly the same as drug. Participants took placebo by mouth for approximately 6 weeks, and after unblinding, they took donepezil hydrochloride for 6 months.
Measure Participants	12	9
Mean (Standard Deviation) [score on a scale]	.003 (1.51)	.17 (2.52)

16. Secondary Outcome

Title	Change on Trail Making Test - Condition
Description	The Delis-Kaplan Executive Function (D-KEFS Trail) Subtest 4: Number-Letter Switching Scaled Score was used to assess executive functioning. Scaled scores range from 1-19. Higher scores represent less impairment (below 8 = low; 8-12 = average; > 12 = above average). Scores represent seconds to complete the task. Faster performance is better.
Time Frame	Baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Drug	Placebo
Arm/Group Description	Participants in the Drug group received oral 5mg of Donepezil Hydrochloride daily for 6 months. The Drug group was assessed at baseline, after approximately 6 weeks. The baseline to 6 weeks phase was part of the double-blind, placebo controlled portion of the trial. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth	Participants in the placebo group first received oral administration of a placebo pill for approximately 6 weeks. After that initial interval, the study was unblinded and participants in the placebo group then received 5mg of donepezil hydrochloride treatment for 6 months. The Placebo group was evaluated at baseline, after 6 weeks of placebo, after 6 weeks of donepezil hydrochloride drug treatment, and 6 months of donepezil hydrochloride treatment. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth Placebo: prepared placebo looking exactly the same as drug. Participants took placebo by mouth for approximately 6 weeks, and after unblinding, they took donepezil hydrochloride for 6 months.
Measure Participants	12	10
Mean (Standard Deviation) [units on a scale]	-1.67 (39.45)	-2.3 (41.46)

17. Secondary Outcome

Title	Change in Visual Form Discrimination
Description	Measure of visuospatial function requiring matching designs from the Benton Visual Form Discrimination test. Total scores is calculated by adding the number of items correct. Total score ranges from 0-32, higher score is better.
Time Frame	Baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Drug	Placebo
Arm/Group Description	Participants in the Drug group received oral 5mg of Donepezil Hydrochloride daily for 6 months. The Drug group was assessed at baseline, after approximately 6 weeks. The baseline to 6 weeks phase was part of the double-blind, placebo controlled portion of the trial. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth	Participants in the placebo group first received oral administration of a placebo pill for approximately 6 weeks. After that initial interval, the study was unblinded and participants in the placebo group then received 5mg of donepezil hydrochloride treatment for 6 months. The Placebo group was evaluated at baseline, after 6 weeks of placebo, after 6 weeks of donepezil hydrochloride drug treatment, and 6 months of donepezil hydrochloride treatment. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth Placebo: prepared placebo looking exactly the same as drug. Participants took placebo by mouth for approximately 6 weeks, and after unblinding, they took donepezil hydrochloride for 6 months.
Measure Participants	12	11
Mean (Standard Deviation) [score on a scale]	.92 (3.09)	.33 (3.94)

18. Secondary Outcome

Title	Change in Category Fluency Test
Description	Measure of language / semantic function. This task requires participants to generate words belonging to specific categories within 1 minute. There are three trials. Total scores is computed by obtaining the mean number of words generated across the three trials (fruits/vegetables/animals). Higher score represents better outcome.
Time Frame	Baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Drug	Placebo
Arm/Group Description	Participants in the Drug group received oral 5mg of Donepezil Hydrochloride daily for 6 months. The Drug group was assessed at baseline, after approximately 6 weeks. The baseline to 6 weeks phase was part of the double-blind, placebo controlled portion of the trial. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth	Participants in the placebo group first received oral administration of a placebo pill for approximately 6 weeks. After that initial interval, the study was unblinded and participants in the placebo group then received 5mg of donepezil hydrochloride treatment for 6 months. The Placebo group was evaluated at baseline, after 6 weeks of placebo, after 6 weeks of donepezil hydrochloride drug treatment, and 6 months of donepezil hydrochloride treatment. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth Placebo: prepared placebo looking exactly the same as drug. Participants took placebo by mouth for approximately 6 weeks, and after unblinding, they took donepezil hydrochloride for 6 months.
Measure Participants	12	10
Mean (Standard Deviation) [score on a scale]	.17 (5.56)	-2.8 (4.02)

19. Primary Outcome

Title	Instrumental Activities of Daily Living
Description	Scale of instrumental activities of daily living (IADLs), adapted from Lawton Brody scale. Caregiver rates 8 functional items from 0-2 severity. Total score is the sum of ratings for each item. Total score ranges from 0 (minimum) to 16 (maximum) with higher scores representing worse functional outcomes.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Drug Treatment
Arm/Group Description	All Participants received Donepezil Hydrochloride daily for 6 months. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth
Measure Participants	23
Mean (Standard Deviation) [units on a scale]	6.54 (4.23)

20. Secondary Outcome

Title	Change in Digit Span Backwards
Description	This measure represents the change in the variable longest Digit Span Backwards (LDSB) from baseline to 6 weeks. Score represents the maximum length of number repeated in the backward condition. Score ranges from 0 to 8. Higher scores represent better outcome.
Time Frame	Baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Drug	Placebo
Arm/Group Description	Participants in the Drug group received oral 5mg of Donepezil Hydrochloride daily for 6 months. The Drug group was assessed at baseline, after approximately 6 weeks and after 6 months of treatment. The baseline to 6 weeks phase was part of the double-blind, placebo controlled portion of the trial. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth	Participants in the placebo group first received oral administration of a placebo pill for approximately 6 weeks. After that initial interval, the study was unblinded and participants in the placebo group then received 5mg of donepezil hydrochloride treatment for 6 months. The Placebo group was evaluated at baseline, after 6 weeks of placebo, after 6 weeks of donepezil hydrochloride drug treatment, and 6 months of donepezil hydrochloride treatment. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth Placebo: prepared placebo looking exactly the same as drug. Participants took placebo by mouth for approximately 6 weeks, and after unblinding, they took donepezil hydrochloride for 6 months.
Measure Participants	12	10
Mean (Standard Deviation) [units on a scale]	0.5 (0.8)	0.1 (0.75)

Adverse Events

Time Frame	6 Months
Arm/Group Title	Drug		Placebo
Arm/Group Description	Participants in the Drug group received oral 5mg of Donepezil Hydrochloride daily for 6 months. The Drug group was assessed at baseline, after approximately 6 weeks and after 6 months of treatment. The baseline to 6 weeks phase was part of the double-blind, placebo controlled portion of the trial. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth		Participants in the placebo group first received oral administration of a placebo pill for approximately 6 weeks. After that initial interval, the study was unblinded and participants in the placebo group then received 5mg of donepezil hydrochloride treatment for 6 months. The Placebo group was evaluated at baseline, after 6 weeks of placebo, after 6 weeks of donepezil hydrochloride drug treatment, and 6 months of donepezil hydrochloride treatment. Donepezil Hydrochloride: 5mg of Donepezil Hydrochloride by mouth Placebo: prepared placebo looking exactly the same as drug. Participants took placebo by mouth for approximately 6 weeks, and after unblinding, they took donepezil hydrochloride for 6 months.
All Cause Mortality
	Drug		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/11 (0%)
Serious Adverse Events
	Drug		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Drug		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/11 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.